Aging is associated with an increased incidence of serum autoantibodies. The presence of such autoantibodies has been reported by some investigators to be associated with shortened survival in man. The goal of this research project is to identify some of the immunologic, genetic and environmental factors that may influence the development of age-associated autoantibodies and autoimmunity in human beings. The specific aims of this project are the following: 1) To analyze the age-associated changes in the frequency and the patterns of expression of autoreactive B cells for human IgG (rheumatoid factor), for human thyroglobulin and for single stranded DNA in the peripheral blood of man following polyclonal activation with the T-dependent B cell stimulator the Epstein-Barr Virus (EBV) and with the T-dependent stimulator pokeweed mitogen (PWM). 2) To analyze the age-associated changes in the avidity, specificity, and heterogeneity of the autoantibodies and how they may compare with those autoantibodies associated with autoimmune disease. 3) To characterize the B lymphocytes inducible by the polyclonal activators to secrete these autoantibodies and the role of regulatory T cells in the control of autoreactive B cell proliferation and autoantibody production associated with aging. Through these experiments we expect to delineate some immunological controlling factors in age-associated increase in autoantibody expression in man and identify factors which can be modulated to control age-associated autoimmunity in man.